Taxonomic distribution of proteins containing FTO_NTD domains

The tree below includes only several representative species and genera. The complete taxonomic breakdown of all proteins containing FTO_NTD domains can be accessed here. Click the counts or percentage values to display the corresponding proteins.

Crystal structure of the FTO protein reveals basis for its substrate specificity.

Han Z, Niu T, Chang J, Lei X, Zhao M, Wang Q, Cheng W, Wang J, Feng Y, Chai J
Nature. 2010; 464: 1205-9

Recent studies have unequivocally associated the fat mass and obesity-associated (FTO) gene with the risk of obesity. In vitro FTO protein is an AlkB-like DNA/RNAdemethylase with a strong preference for 3-methylthymidine (3-meT) insingle-stranded DNA or 3-methyluracil (3-meU) in single-stranded RNA. Here wereport the crystal structure of FTO in complex with the mononucleotide 3-meT. FTOcomprises an amino-terminal AlkB-like domain and a carboxy-terminal domain with anovel fold. Biochemical assays show that these two domains interact with eachother, which is required for FTO catalytic activity. In contrast with thestructures of other AlkB members, FTO possesses an extra loop covering one sideof the conserved jelly-roll motif. Structural comparison shows that this loopselectively competes with the unmethylated strand of the DNA duplex for bindingto FTO, suggesting that it has an important role in FTO selection againstdouble-stranded nucleic acids. The ability of FTO to distinguish 3-meT or 3-meUfrom other nucleotides is conferred by its hydrogen-bonding interaction with the two carbonyl oxygen atoms in 3-meT or 3-meU. Taken together, these resultsprovide a structural basis for understanding FTO substrate-specificity, and serveas a foundation for the rational design of FTO inhibitors.